Differential expression and distribution of focal adhesion and cell adhesion molecules in rat hepatocyte differentiation

The present study has examined the distribution of axons of differing sizes in the optic pathway of the ground squirrel. Axon diameters were measured from electron micrographs at various locations across sections of the optic nerve and tract, and total distributions and numbers were estimated. In both the nerve and tract, roughly 1.2 million optic axons were present. The population of optic axons had a unimodal size distribution, peaking at 0.9 microm in diameter and having an extended tail toward larger diameters. Local axon diameter distributions in the optic tract indicated distinct (though partially overlapping) axon diameter classes, including one of fine sizes peaking at 0.8-0.9 microm, a second of medium sizes peaking around 1.7-1.8 microm, and a third composed of the larger fibers with diameters up to 4.8 microm. The fine-caliber axons were found at all locations in the tract, and were the only axons present immediately adjacent to the pia, while the medium- and coarse-caliber axons were found at deeper locations. Curiously, the larger axons were found primarily in the medial parts of the tract, where axons from the dorsal retina normally course. A similarly restricted distribution of the larger axons was observed in the dorsotemporal parts of the optic nerve, suggesting that this difference in the tract may relate to an asymmetric distribution of ganglion cells on the retina giving rise to these axons. Measurements of axonal size taken within the optic fiber layer in dorsal and ventral parts of the retina confirmed this asymmetry, consistent with previous demonstrations of soma size differences in the dorsal versus ventral retina. The partial segregation of axons by size in the optic tract of the ground squirrel then reflects both the asymmetric distribution of retinal ganglion cell classes and the chronotopic reordering of optic axons that occurs within the chiasmatic region.     

Premedication with oral midazolam in children--an assessment of psychomotor function, anxiolysis, sedation and pharmacokinetics

We studied 30 children, aged 4 to 12 years, undergoing elective circumcision, premedicated with midazolam 0.5 mg.kg-1 and atropine 0.02 mg.kg-1 by mouth. A modified postbox test and the coding component of the Wechsler intelligence scale (WISC-R) was used to assess the preoperative effect of premedication on psychomotor function. Mood and sedation were also scored and related to serum midazolam concentrations. The children showed a significant decline in psychomotor performance 30 and 60 minutes after premedication when compared with their best unmedicated performance recorded the previous evening. This decline in psychomotor performance was only weakly associated with serum midazolam concentrations (r = 0.1). The postbox toy ratio is a suitable measurement of psychomotor performance in children because of its simplicity and ease of use in the clinical environment, although it may suffer the "test-retest" limitations of similar types of assessment. The sedative and anxiolytic effects of midazolam provide a quiet environment for a smooth induction of anaesthesia.     

Treatment of acute lymphoblastic leukemia. 30 years' experience at St. Jude Children's Research Hospital

BACKGROUND: Therapy for childhood lymphoblastic leukemia has evolved during the past three decades, but key questions about what are the least toxic, most effective forms of treatment remain unanswered because of the lack of comprehensive follow-up information. METHODS: To assess long-term outcome in the series of clinical trials conducted at St. Jude Hospital, we compared the results of treatment typical of four eras: exploratory combination chemotherapy (era 1, 1962 to 1966; 91 patients), regimens for the control of meningeal leukemia (era 2, 1967 to 1979; 825 patients), limited intensification of therapy (era 3, 1979 to 1983; 428 patients), and extended intensification of therapy (era 4, 1984 to 1988; 358 patients). ("Intensification" refers to strategies of systemic chemotherapy that are more aggressive than conventional ones.) The major end points were survival and event-free survival; we also calculated the relative risk of treatment failure and the rate of relapse or death after treatment ended (post-treatment failure rate). RESULTS: The probability of event-free survival improved significantly in each successive era (P < 0.001 by the log-rank test), reaching 71 percent in era 4. There was a decrease of approximately 50 percent in the risk of treatment failure from one era to the next in each subgroup of patients defined according to different combinations of the leukocyte count, race, age, and sex. Leukemia appeared to be eradicated in patients who remained in complete remission for three years or more after treatment in era 4. The incidence of death due to nonleukemic causes remained 4 to 6 percent despite the trend toward more intensive treatment. An estimated 765 patients (45 percent) are long-term survivors; most of them (80 percent) have no health problems related to leukemia or its treatment. CONCLUSIONS: The development and successful application of preventive therapy for meningeal leukemia, followed by the intensification of systemic chemotherapy, has progressively improved the rate of cure of childhood lymphoblastic leukemia, with relatively few adverse sequelae.     

Bronchoalveolar lavage. Quantitation of intraalveolar fluid?

A precise calculation of the amount of intraalveolar fluid is the basis of a quantitative analysis of intraalveolar compounds. Different approaches have been made to cover this important problem. Here, we report a comparative study with five markers: 99mTc-DTPA, 51Cr-EDTA, inulin, urea, and methylene blue in animal experiments as well as in human experiments. The marker substances were added to the lavage fluid, and the "dilution" of the markers, i.e., the alveolar fluid, was calculated. The results showed that in animals with healthy lungs the tracer methods are able to calculate amounts of intraalveolar fluid that are comparable to morphologic findings. In animals as well as in humans, methylene blue and inulin were shown to be useless in determining alveolar fluid volume compared with the tracer methods. In humans, the calculations with the urea method and with Tc-DTPA were in the same magnitude, but there was no individual correlation. We conclude that, at present, the methods to quantitate alveolar fluid volume lack precision and add nothing to a deeper understanding of alveolar biology.     

Reconstruction of graphs based on random walks

The analysis of complex networks is of major interest in various fields of science. In many applications we face the challenge that the exact topology of a network is unknown but we are instead given information about distances within this network. The theoretical approaches to this problem have so far been focusing on the reconstruction of graphs from shortest path distance matrices. Often, however, movements in networks do not follow shortest paths but occur in a random fashion. In these cases an appropriate distance measure can be defined as the mean length of a random walk between two nodes — a quantity known as the mean first hitting time.In this contribution we investigate whether a graph can be reconstructed from its mean first hitting time matrix and put forward an algorithm for solving this problem. A heuristic method to reduce the computational effort is described and analyzed. In the case of trees we can even give an algorithm for reconstructing graphs from incomplete random walk distance matrices.     

Concerns of the dry-cleaning industry: a qualitative investigation of labor and management

BACKGROUND: Occupational scientists agree there are hazards associated with dry-cleaning, but do dry-cleaning owners and workers concur? Knowledge of owners' and workers' perceptions can help guide intervention efforts to reduce worker exposure. To better understand these issues, a qualitative study was conducted using focus group methodology and constant comparative analysis. METHODS: Two owner and four worker focus groups were held. RESULTS: Findings suggest that overall, health and safety issues were not of great concern. Owners were primarily concerned with the economic impact of regulations. Workers did express some anxiety about solvent exposure and burns, but most felt that these hazards were "just part of the job." Also, other than the installation of air-conditioning in the shops and the provision of health benefits, workers could not think of ways health and safety on the job could be improved. CONCLUSIONS: These findings will be used to develop comprehensive safety and health interventions (e.g., engineering plus education and training) in dry-cleaning shops.     

Blood-brain barrier carrier-mediated transport and brain metabolism of amino acids

We have examined the effects of the macrocyclic lactone protein kinase C (PKC) activator bryostatin 1 on taxol-induced apoptosis and inhibition of clonogenicity in the human monocytic leukemia cell line U937. Exposure of cells to bryostatin 1 (10 nM; 15 hr) after (but not before) a 6-hr incubation with 0.5 microM taxol significantly increased apoptosis and resulted in an approximately 3 log reduction in clonogenicity. Cell cycle analysis revealed that the increase in apoptotic cells following bryostatin 1 treatment occurred primarily in the population undergoing taxol-mediated G2M arrest. The actions of bryostatin 1 were not attributable to potentiation of taxol-induced tubulin stabilization or to a reduction in the intracellular retention of taxol. Following exposure of cells to taxol, the Bcl-2 protein displayed an alteration in mobility that was not modified appreciably by bryostatin 1 treatment. The mobility shift in Bcl-2 protein from cells exposed to taxol followed by bryostatin 1 was eliminated by treatment of lysates with the protein phosphatase 2A (PP2A); the latter effect was blocked by okadaic acid. Treatment of cells with taxol followed by bryostatin 1 did not increase the amount of total Bax (compared with treatment with taxol alone), but did increase the amount of free Bax in the supernatant fraction. Finally, the ability of bryostatin 1 to potentiate taxol-induced apoptosis in U937 cells was mimicked closely by 2'-amino-3'-methoxyflavone (PD98059), a specific inhibitor of the mitogen-activated protein kinase (MAPK) kinase (MEK). Collectively, these findings indicate that bryostatin 1 increases the susceptibility of U937 cells to taxol-induced apoptosis and inhibition of clonogenicity. They also raise the possibility that this phenomenon may involve functional alterations in Bcl-2 and/or other proteins involved in regulation of the cell death pathway.     

Altered release of prostaglandins by opioids contributes to impaired cerebral hemodynamics following brain injury

OBJECTIVES: After fluid percussion brain injury (FPI) in the newborn pig, pial arteries constrict and responses to dilator stimuli, including opioids, are blunted. This study was designed to determine if altered release of prostaglandins contributes to blunted opioid dilation of cerebral arteries in newborn piglets following brain injury. DESIGN: Prospective, in vivo, cerebral hemodynamic animal study. SETTING: University research laboratory. SUBJECTS: Newborn (1- to 5-days old) piglets of either gender. INTERVENTIONS: In anesthetized, newborn, 1- to 5-day-old pigs, a closed cranial window was used to measure pial artery diameter and to collect cortical periarachnoid cerebrospinal fluid (CSF) for determination of 6-keto-PGF1alpha, the stable metabolite of prostaglandin I2 (PGI2) and thromboxane B2 (TXB2), the stable metabolite of TXA2, via radioimmunoassay. FPI of moderate severity (1.9 to 2.3 atmospheres) was produced by using a pendulum to strike a piston on a saline-filled cylinder that was fluid coupled to the brain via a hollow screw inserted through the cranium. MEASUREMENTS AND MAIN RESULTS: Methionine enkephalin (Met) vasodilation was blunted after FPI but was partially restored with indomethacin pretreatment (5 mg/kg i.v.) (8 +/- 1 [SEM] %, 13 +/- 1%, and 20 +/- 1% vs. 1 +/- 1%, 3 +/- 1%, and 5 +/- 1% vs. 7 +/- 1%, 10 +/- 1%, and 15 +/- 1%, respectively, for 10(-10), 10(-8), and 10(-6) M Met during control conditions, after FPI, and after FPI pretreated with indomethacin, n = 6). Similarly, restoration of Met dilation after FPI was observed with SQ 29,548, a TXA2 antagonist. Met-induced 6-keto-PGF1alpha release was blunted following FPI (889 +/- 20, 1130 +/- 33, and 1886 +/- 59 vs. 2630 +/- 36, 2775 +/- 30, and 2825 +/- 36 pg/mL for control, 10(-10), and 10(-6) M Met before and after FPI, respectively, n = 6). In contrast, Met-induced TXB2 release was enhanced after FPI (340 +/- 20, 423 +/- 25, and 473 +/- 30 pg/mL vs. 518 +/- 30, 726 +/- 90, and 901 +/- 35 pg/mL for control, 10(-10), and 10(-6) M Met before and after FPI, respectively, n = 6). Leucine enkephalin- and dynorphin-induced dilation and associated prostaglandin release were similarly altered following FPI. Beta endorphin-induced constriction was enhanced following FPI, and these potentiated responses were blunted after indomethacin or SQ 29,548 pretreatment. CONCLUSIONS: These data show that FPI increases CSF 6-keto-PGF1alpha and TXB2 concentrations. These data suggest that altered release of prostaglandins by opioids contribute to impaired cerebral hemodynamics following FPI in piglets.     

Double free-flap reconstruction of massive defects involving the lip, chin, and mandible

Men develop perioperative ulnar neuropathies more frequently than women. To determine the role of anatomical gender differences in the development of these neuropathies, we performed several studies of the anatomy of the ulnar nerve, cubital tunnel, and elbow region. These studies included detailed dissection of male and female embalmed and unembalmed cadavers, ultrasound measurements of the tissue layers at the elbow, and measurement of various dimensions of the coronoid process of the ulna in multiple skeletal sets. No gross anatomical differences were found between genders regarding the course of the ulnar nerve through the upper limb. However, there was a strikingly larger (2-19 times greater) fat content on the medial aspect of the elbow in women compared to men, and the tubercle of the coronoid process was approximately 1.5 times larger in men (P < or = .002, rank sum test). Our finding suggest that the tubercle of the coronoid process is a likely area for external compression-induced ischemia of the ulnar nerve because the nerve and its arterial supply (the posterior ulnar recurrent artery) are covered at the tubercle only by skin, subcutaneous fat, and a very thin aponeurosis of the flexor carpi ulnaris. Importantly, this tubercle is larger and the nerve and blood vessels passing by it are less protected by subcutaneous fat in men than in women. These two anatomical differences between men and women may contribute to the increased frequency of perioperative ulnar neuropathy induced by external pressure at the medial aspect of the elbow in men.